To the Editor: In his review article on drug therapy for hepatitisB virus (HBV) infection, Dienstag (Oct. 2 issue)1 does not mentionthe use of prophylactic antiviral drugs in patients treatedwith chemotherapy, stem-cell transplantation, or immunosuppressiveagents. Reactivation of hepatitis B (including death2) has beendescribed in patients who were anti–hepatitis B core–positiveand hepatitis B surface antigen (HBsAg)–negative.3 Severalguidelines and discussions4,5 on this topic have been published,recommending lamivudine as prophylaxis. This is an importantissue that should have been included in the review article becausethere is an increasing population of patients who are at riskfor this threatening complication.
Juan Miguel Bergua, M.D. Carmen Cabrera, M.D. Helena Bañas, M.D. Hospital San Pedro de Alcántara 10003 Cáceres, Spain jmbergua{at}terra.es
References
Dienstag JL. Hepatitis B virus infection. N Engl J Med 2008;359:1486-1500. [Free Full Text]
Gwak GY, Koh KC, Kim HY. Fatal hepatic failure associated with hepatitis B virus reactivation in a hepatitis B surface antigen-negative patient with rheumatoid arthritis receiving low dose methotrexate. Clin Exp Rheumatol 2007;25:888-889. [Web of Science][Medline]
Targhetta C, Cabras MG, Mamusa AM, Mascia G, Angelucci E. Hepatitis B virus-related liver disease in isolated anti-hepatitis B-core positive lymphoma patients receiving chemo- or chemo-immune therapy. Haematologica 2008;93:951-952. [Free Full Text]
Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008;148:519-528. [Free Full Text]
Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007;136:699-712. [Erratum, Br J Haematol 2007;137:81.] [CrossRef][Web of Science][Medline]
To the Editor: We believe it would be relevant to stress thatnucleotide and nucleoside analogues can prevent HBV reactivationin patients undergoing immunosuppression who have either inactivedisease (HBsAg-positive, hepatitis B e antigen [HBeAg]–negative,anti-HBe–positive, normal aminotransferase levels, HBVDNA of <20,000 IU per milliliter, and anti–hepatitisB core IgM–negative) or occult disease (HBsAg-negative,with markers of previous HBV contact [i.e., isolated hepatitisB core antigen]).1 HBV reactivation is a known and feared complicationin patients who are undergoing immunosuppressive regimens thatfavor viral replication and, consequently, widespread hepatocyteinfection. After immunocompetence is regained, immunomediatedhepatic damage develops, leading to acute hepatitis or hepaticfailure.2 Reactivation has also been described in patients receivingimmunosuppressive agents such as glucocorticoids, azathioprine,and infliximab in various clinical settings (gastroenterology,dermatology, oncology, and rheumatology).1 Preemptive treatmentwith nucleotide and nucleoside analogues effectively reducesthe risk of HBV reactivation in hematology patients,3 even ifprotocols and the issue of treating occult carriers are stilldebated.4 The search for inactive or occult HBV infection shouldbe mandatory in all patients undergoing immunosuppression, sinceeffective prophylaxis is now available.
Massimo Marignani, M.D. M. Christina Cox, M.D. Gianfranco Delle Fave, M.D. University La Sapienza 00189 Rome, Italy mmarignani{at}hotmail.com
References
Marzano A, Angelucci E, Andreone P, et al. Prophylaxis and treatment of hepatitis B in immunocompromised patients. Dig Liver Dis 2007;39:397-408. [CrossRef][Web of Science][Medline]
Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 2001;120:1009-1022. [CrossRef][Web of Science][Medline]
Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med 2008;148:519-528. [Free Full Text]
Cox MC, Marignani M, Veggia B, et al. Is management with lamivudine always the appropriate choice for HBV patients with onco-hematologic diseases? Ann Hematol 2008 September 20 (Epub ahead of print).
To the Editor: In his report on the worldwide prevalence ofHBV infection, Dienstag places Italy among countries with amedium endemic level (defined as a prevalence of HBsAg of >2%).Actually, the epidemiology of HBV infection has changed markedlyin Italy during the past three decades. In the early 1980s,Italy was a country with a medium endemic level, with an HBsAgprevalence of 3.4%. The prevalence dropped to 1.6% in 1990.1Currently, Italy is at a very low endemic level, with an HBsAgprevalence of less than 1%, as clearly stated by some surveys,which were performed from 1994 through 2008 (Table 1).2,3 Atthe same time, a decrease in the prevalence of HBeAg and hepatitisdelta positivity was observed among HBV carriers.
Table 1. Prevalence of Hepatitis B Surface Antigen (HBsAg) in Italy, According to Recent Surveys.
Since 1991, HBV vaccination has been mandatory in Italy forall newborns and adolescents, and coverage of 94% has been reached.According to the National Surveillance System, the incidenceof acute HBV infection per 100,000 inhabitants declined from5.1 in 1991 to 1.3 in 2005.4
Laura Milazzo, M.D. Spinello Antinori, M.D. University of Milan 20157 Milan, Italy laura.milazzo{at}unimi.it
References
D'Amelio R, Matricardi PM, Biselli R, et al. Changing epidemiology of hepatitis B in Italy: public health implications. Am J Epidemiol 1992;135:1012-1018. [Free Full Text]
Da Villa G, Romanò L, Sepe A, et al. Impact of hepatitis B vaccination in highly endemic area of south Italy and long-term duration of anti-HBs antibody in two cohorts of vaccinated individuals. Vaccine 2007;25:3133-3136. [CrossRef][Web of Science][Medline]
Fabris P, Baldo V, Baldovin T, et al. Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population. J Clin Gastroenterol 2008;42:527-532. [CrossRef][Web of Science][Medline]
Mele A, Tosti ME, Mariano A, et al. Acute hepatitis B 14 years after the implementation of universal vaccination in Italy: areas of improvement and emerging challenges. Clin Infect Dis 2008;46:868-875. [CrossRef][Web of Science][Medline]
The author replies: Bergua et al. and Marignani et al. pointout the importance of beginning antiviral therapy preemptivelyin patients with HBV infection (whether active, inactive, oreven recovered) who undergo immunosuppressive chemotherapy,without which HBV reactivation can result in substantial morbidityand mortality. My brief review of antiviral therapy for HBVinfection had space constraints, which prevented me from addressingthe topic of patients with therapeutic immunosuppression, aswell as other special populations (e.g., children, pregnantwomen, organ-allograft recipients, and patients with renal failureor extrahepatic disease). For a thorough overview of antiviraltherapy in these specific populations in general and in immunosuppressedpatients in particular, readers should consult comprehensivepractice guidelines issued by national organizations,1,2 aswell as the October 2008 proceedings of the National Institutesof Health Consensus Development Conference on Management ofHepatitis B.3
I thank Milazzo and Antinori for pointing out the decliningprevalence of HBV infection in Italy, a pattern evolving inother countries with either a low or moderate prevalence duringthe contemporary era of HBV vaccination. My intent in showingthe world map of HBV prevalence was to emphasize the differencein clinical expression of HBV infection on the basis of thetime in life when the infection is acquired. This factor, inturn, is a reflection of the prevalence of the infection inthe general population, with a high prevalence in countriesin which there is primarily perinatal infection and a low prevalencein countries in which there is primarily adult infection. Iwas not able to update the current world map on a country-by-countrybasis and relied instead on data in the public domain derivedfrom the Centers for Disease Control and Prevention (CDC).4On September 19, 2008, 2 weeks before the publication of myarticle in the Journal, the CDC published an updated world mapshowing the prevalence of HBV infection, in which Italy wascategorized as a low-prevalence country.5 A corrected versionof the world map in my article, which also corrects other areasin western and northern Europe, is available at NEJM.org.
Jules L. Dienstag, M.D. Massachusetts General Hospital Boston, MA 02114 jdienstag{at}partners.org
References
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507-539. [Erratum, Hepatology 2007;45:1347.] [CrossRef][Web of Science][Medline]
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2008 October 29 (Epub ahead of print).
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). 1. Immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54:1-31. [Erratum, MMWR Morb Mortal Wkly Rep 2006;55:158-9, 2007;56:1267.] [Medline]
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep 2008;57:1-20. [Medline]
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